To further substantiate our recent findings in rats that activation of the renal kallikrein-kinin system (KKS) may constitute an important mechanism for the antihypertensive function of the contralateral kidney during benign 2-kidney, 1-clip (2K-1C) hypertension and that chronicity of hypertension impairs this system, changes in blood pressure and renal excretory function in response to inhibitors of the KKS infused intrarenally into the contralateral kidneys of conscious dogs before and after induction of 2K-1C hypertension will be determined to assess the functional status of this vasodepressor-natriuretic system during the course of hypertension. Blood pressure responses to various pharmacological manipulations of the KKS will also be assessed after induction of benign 2K-1C hypertension in conscious Sprague-Dawley and Wistar-Kyoto rats, as well as Wistar-Kyoto rats bearing a contralateral, kallikrein-deficient kidney transplanted from a spontaneously hypertensive rat of the Okamoto-Kyoto strain. In addition, experiments will be undertaken to identify the nature of the stimulus for activating the KKS of the contralateral kidney during 2K-1C hypertension.